Original Paper
Cerebrovasc Dis 2013;35:444–450
DOI: 10.1159/000348704
Complications of Acute Stroke and
the Occurrence of Early Seizures
Alessandro Pezzini a Mario Grassi b Elisabetta Del Zotto a Alessia Giossi a
Irene Volonghi a Paolo Costa a Loris Poli a Andrea Morotti a Massimo Gamba c
Marco Ritelli d Marina Colombi d Alessandro Padovani a
a
Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia,
b
Dipartimento di Sanità Pubblica, Sezione di Statistica Medica e Epidemiologia, Università di Pavia, Pavia,
c
  Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, and d Divisione di Biologia e Genetica,
Dipartimento di Scienze Biomediche e Biotecnologie, Università degli Studi di Brescia, Brescia, Italia
Key Words
Epilepsy · Stroke · Complications of stroke · Epidemiology
of stroke
Abstract
Background: Seizures are common neurological conse-
quences of stroke. Although a number of factors including
stroke severity on admission, cortical involvement, and
stroke subtype have been consistently associated with
post-stroke seizures, the effect that medical and neurologi-
cal complications of stroke, occurring in the very acute
phase, might have on such a risk has never been adequate-
ly explored. In the present study we aimed at determining
the extent to which complications within the first week of
stroke influence the risk of early seizures (ES). Methods:
Data of consecutive patients with first-ever acute stroke in-
cluded in the Brescia Stroke Registry were analyzed. ES
(≤7 days) were recorded and correlated with demographic
data, disease characteristics, risk factors, and prespecified
medical and neurological stroke complications in a multi-
variate path analysis model. Results: 516 patients with first-
ever acute stroke were eligible for inclusion in the present
study. Of them, 436 patients had ischemic stroke (IS) [64
© 2013 S. Karger AG, Basel
1015–9770/13/0355–0444$38.00/0
E-Mail karger@karger.com
www.karger.com/ced
Received: December 17, 2012
Accepted: January 31, 2013
Published online: May 31, 2013
(14.6%) with hemorrhagic transformation (HT)] and 80 had
intracerebral hemorrhage (ICH). Twenty patients (3.9%) de-
veloped ES. Patients with ES had a higher burden of compli-
cations compared with those without (30 vs. 4.2%, for pa-
tients with >6 complications). Lesion type, stroke complica-
tions, and lesion site were directly related to the risk of
seizure occurrence (OR, 0.24; 95% CI, 0.07–0.80 for IS vs. ICH;
OR, 1.57; 95% CI, 1.21–2.01 for any increase of 1 in the num-
ber of complications; OR, 0.15; 95% CI, 0.04–0.56 for subcor-
tical lesions vs. cortical lesions). Complications appeared
also to mediate the indirect effect of lesion type on the oc-
currence of ES (OR, 0.75; 95% CI, 0.60–0.94). No significant
difference on the risk of ES was observed when HT and ICH
were compared. The total effect of lesion type was 0.25 ×
0.75 = 0.18, corresponding to (1–0.18) = 82% lower risk of
ES for IS as compared to ICH. Conclusion: Although major
determinants of ES are nonmodifiable, preventable and
treatable medical and neurologic complications within the
first week of stroke increase the risk of ES and mediate the
effect of established predictors on the propensity to post-
stroke epilepsy. Future epidemiologic studies aimed at in-
vestigating post-stroke seizures should include precise in-
formation on these complications.
Copyright © 2013 S. Karger AG, Basel
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Univ.degli Studi di Brescia
Alessandro Pezzini
Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica
Università degli Studi di Brescia, P. le Spedali Civili, 1
Downloaded by:
IT–25100 Brescia (Italy)
E-Mail alessandro.pezzini @ med.unibs.it
 Introduction
Seizures are well-known and potentially serious neu-
rological complications of acute stroke [1–3]. Despite the
methodological differences among the studies conducted
so far aimed at investigating this topic, a number of fac-
tors have been consistently associated with the occur-
rence of post-stroke seizures and epilepsy, especially
within the first week. These include stroke subtype (isch-
emic or hemorrhagic), size, location, and severity of the
vascular lesion. A limitation of all these studies is that they
did not evaluate the impact that complications of stroke,
occurring in the very acute phase, might have on such a
risk. Actually, patients with acute stroke are vulnerable to
the development of various complications, both neuro-
logic and medical, as a direct consequence of the brain
injury itself, of the disability caused by the stroke, or of
stroke-related treatments [2–4]. Not only these complica-
tions after stroke are common as well as related to delayed
successful rehabilitation and poor outcome, but they can
also start a vicious cycle which ends up in further compli-
cations. In this regard, at least theoretically, it cannot be
excluded a priori that complications occurring soon after
stroke onset make these patients more susceptible to de-
velop seizures. This hypothesis has never been adequate-
ly explored in previous studies [5].
We therefore sought to determine the impact of se-
lected neurologic and medical complications of stroke on
the development of early seizures (ES) in a prospective
cohort of acute stroke patients.
Subjects and Methods
Data were collected within the Brescia Stroke Registry, an on-
going, hospital-based, longitudinal cohort study of acute stroke
patients from the contiguous catchment area. The study was ap-
proved by the Institutional Ethical Standards Committee on hu-
man experimentation. Written informed consent was obtained
from all patients (or next of kin). All patients consecutively admit-
ted to our Department between April 2007 and February 2010 with
symptoms suggestive of acute stroke were screened for inclusion.
Patients were included in the Registry if they fulfilled the following
criteria: (1) a diagnosis of acute stroke according to the World
Health Organization’s definition of stroke; (2) CT/MRI scan re-
sults with no evidence of other causes that might explain the neu-
rologic deficits (e.g. tumor, trauma, infection, or vasculitis). All
patients received an initial diagnostic evaluation and treatment
based on established guidelines [6, 7]. The characteristic features
are a standardized protocol for acute evaluation, monitoring, and
medical treatment with a focus on physiologic homeostasis, a strat-
egy for early mobilization, a multidisciplinary team, and integra-
tion of medical care, nursing, and rehabilitation, with a strong fo-
Post-Stroke Seizures
cus on prevention of complications, including swallowing evalua-
tion before feeding, ultrasound assessment of urine retention, and
intermittent catheterization when needed.
Demographic and Medical Characteristics
Demographic data (age, sex) and history of established vascular
risk factors were retained from each subject. Information was also
recorded on prestroke functional and disease status, drug treat-
ment, and hormonal status in women (online suppl. list; for all on-
line suppl. material, see www.karger.com/doi/10.1159/000348704).
Recurrent stroke, personal history of seizures, onset of symptoms
more than 24 h from admission, subarachnoid hemorrhage, cere-
bral vein thrombosis and transient ischemic attack were considered
exclusion criteria for the present analysis.
Clinical and Biologic Assessment
We evaluated the severity of neurologic deficits by using the Na-
tional Institutes of Health Stroke Scale (NIHSS) [8]. All admission
CT scans were reviewed by stroke neurologists blinded to all clinical
data to determine the location of the vascular lesion, which was clas-
sified as cortical or subcortical. A lesion located to the cortex (with
or without involvement of subcortical white matter) was defined as
cortical, whereas any lesion selectively involving the internal cap-
sule, thalamus, basal ganglia, brainstem or cerebellum was defined
as subcortical. We also collected data on leukoaraiosis, which was
defined as ill-defined and moderately hypodense areas of ≥5 mm
of deep white matter according to previously published criteria [9].
Assessment of Complications
During the first week after admission, 12 prespecified compli-
cations were recorded for all patients after daily examinations, per-
formed by specially trained physicians, nurses, and physiothera-
pists. The definitions of complications are reported in table 1. In
addition, we assessed the occurrence of early hemorrhagic trans-
formation (HT) in patients with cerebral infarct on repeated CT
examination performed after 5 days (±2) from stroke onset or im-
mediately in case of clinical worsening. HT was defined as any de-
gree of hyperdensity within the area of low attenuation [10]. For
the purpose of the present study, complications were considered
to have a causal role when they were detected before the occur-
rence of epileptic seizures. Only these complications were included
in the analysis.
Epileptic Seizures
Seizure recording was based on clinical diagnosis. Seizures
were defined according to the International League against
Epilepsy (ILAE) as paroxysmal disorders of the CNS with or with-
out loss of consciousness or awareness and with or without motor
involvement [11]. Seizures were classified as focal or generalized
(including focal seizures with secondary generalization). Status
epilepticus was defined as unremitting seizure activity or a series
of seizures lasting for more than 5 min [12] and classified as con-
vulsive or nonconvulsive according to clinical and electroenceph-
alographic findings. ES were defined according to the ILAE guide-
lines as those occurring within 7 days of stroke [13].
Statistical Analyses
Descriptive differences among groups were examined with the
χ2 test and one-way ANOVA F test, when appropriate. To explore
the mechanisms involved in the development of ES, we designed a
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Table 1. Definitions of selected complications

Infections
Urinary tract infection Clinical symptoms combined with a positive urinary culture
Chest infection (pneumonia) Respiratory rates combined with at least 1 of the following: temperature >38°C, new
purulent sputum, or positive chest radiograph
Other infection Clinical symptoms, signs or both associated with specific system and positive microbio-
logical cultures or radiographic or other imaging investigation indicating an infection
other than in the chest or urinary tract
Fever Temperature ≥38.0°C at any time
Clinical deterioration
Increased intracranial pressure Imaging evidence of mass effect or brain shift syndrome with clinical deterioration
requiring specific treatment
Stroke recurrence New onset of focal or neurologic deficits that cannot be attributed to the presenting lesion
and are consistent with World Health Organization definitions of stroke
Cardiovascular complications
Pulmonary embolism Clinical diagnosis confirmed by CT scan
Myocardial infarction Elevated troponin T level (0.06 mmol/l) associated with symptoms of ischemia and ECG
changes indicative of new ischemia (new ST–T changes or new left bundle branch block) or
new regional wall motion abnormality on echocardiography
Cardiac failure, arrhythmias Clinical diagnosis by a cardiologist and/or ECG monitoring or Holter evidence
Gastrointestinal
Gastrointestinal bleeding Record of coffee grounds aspirate from nasogastric tube and/or positive fecal occult blood
Dysphagia Inability to drink 90 ml of water without coughing and requiring nasogastric tube
Miscellaneous Other documented complication resulting in a specific medical or surgical intervention
(e.g. constipation, unexplained anemia, urinary retention, electrolyte abnormalities)

path diagram based on a preliminary linear/logistic regression anal-
ysis and clinical evidence. In particular, we investigated the recur-
sive relationships between the following variables: lesion type [isch-
emic stroke (IS), HT or intracerebral hemorrhage (ICH)], lesion site
(cortical or subcortical), acute stroke complications (0–12 accord-
ing to the number of selected complications), changes in stroke se-
verity (NIHSS score changes within the first week after stroke oc-
currence), and ES, adjusted for confounding variables (age, sex, and
NIHSS score on admission). Path analysis is a special type of struc-
tural equation modeling [14], a multivariate approach based on the
use of a system of simultaneous equations to describe a priori path
relationships that generate the data. The causal mechanism of a path
analysis model distinguishes 3 types of effects: direct, indirect, and
total effect with respect to a specific model. The direct effect of an
explanatory (exogenous) variable on a response (endogenous) vari-
able is the net effect of a predictor, compared to the other predictors
in the built-in equations; the indirect effect is the effect mediated by
the pathway relationships of the other variables, and the total effect
is the sum of both the direct and indirect effects. A variable is exog-
enous if its causes lie outside the model, and endogenous when it is
determined by other variables within the model. Lesion type and
site were exogenous variables, while complications, severity and ES
were endogenous variables. We evaluated the model fitting proce-
dure by comparing the observed covariance matrix with the fitted
model covariance matrix. We considered goodness-of-fit indices
(comparative fit index and Tucker-Lewis index), and badness-of fit
indices (root mean square error of approximation and standardized
root mean square residual). Comparative fit index >0.95, Tucker-
Lewis index >0.90, root mean square error of approximation >0.05,
and standardized root mean square residual <0.05 were retained for
‘adequate approximation’ fitting of the model to data [14]. The
structural equations parameters, odds ratios (OR), or mean differ-
ences of the binary or continuous response variables on binary ex-
plicative variables, and average changes of continuous response
variables for unitary change of explicative continuous variables,
were computed by maximum likelihood estimates. The p values of
the direct, indirect, and total estimates were evaluated by Z tests (=
estimate/standard error). p values <0.05 in two-sided tests were
considered statistically significant. Descriptive and exploratory sta-
tistics were evaluated by the SPSS version 15 software (www.spss.
com). Structural equation modeling was fitted with Mplus version
6.12 software (www.statmodel.com).
Results
A total of 1,130 patients with suspected acute stroke
were screened for inclusion during the recruitment period.
Six-hundred and fourteen patients were excluded because
of a diagnosis other than stroke (120 patients), arrival after
24 h from stroke onset (301 patients), subarachnoid hem-
orrhage or cerebral vein thrombosis (56 patients), tran-
sient ischemic attack (124 patients), or personal history of
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Table 2. Demographic and clinical characteristics of the study Table 3. Distribution of ES predictors in the subgroup of stroke
group by stroke subtype patients with and without ES

Ischemic Hemorrhagic Intracerebral Stroke Stroke p value

stroke transformation hemorrhage patients patients
(n = 372) of the infarct (n = 80) without ES with ES
(n = 64) (n = 496) (n = 20)

Mean age ± SD, years 65.5±15.2 68.7±12.9 68.4±13.3 Lesion type

Sex male 224 (60.2) 44 (68.8) 46 (57.5) IS 365 (73.6) 7 (35.0) <0.001
BMI >30 55 (14.7) 9 (14.0) 9 (11.2) HT of the infarct 59 (11.9) 5 (25.0)
Barthel index <75 10 (2.7) 4 (6.2) 3 (3.8) ICH 72 (14.5) 8 (40.0)
Hypertension 237 (63.7) 42 (65.6) 61 (76.2) Lesion site
Diabetes mellitus 67 (18.0) 17 (26.6) 19 (23.8) Cortical 204 (41.1) 17 (85.0) <0.001
Hypercholesterolemia 136 (36.6) 20 (31.2) 23 (28.8) Number of complications
Current smoking* 95 (25.5) 8 (12.5) 12 (15.0) 0–2 289 (58.3) 4 (20.0) <0.001
Alcohol intake excessive 22 (5.9) 2 (3.1) 8 (10.0) 3–4 122 (24.6) 6 (30.0)
Oral contraceptivesa 6 (33.0) 0 (0.0) 0 (0.0) 5–6 64 (12.9) 4 (20.0)
Estrogen replacement
7 or more 21 (4.2) 6 (30.0)
therapyb 6 (4.8) 1 (6.7) 1 (3.4) NIHSS score
Ischemic heart disease 57 (15.3) 12 (18.8) 7 (8.8)
On admission 8.45±6.88 13.3±8.19 <0.001
Atrial fibrillation* 99 (26.6) 26 (40.6) 17 (21.2)
At 2 days 7.25±6.74 13.6±7.73
Venous
At 4 days 6.76±6.67 13.7±8.20
thromboembolism 12 (3.2) 2 (3.1) 2 (2.5)
Peripheral arterial At 7 days 5.53±6.18 11.8±7.77
disease 25 (6.7) 3 (4.7) 3 (3.8) Data are expressed as numbers with percentages in parentheses
Antiplatelets 115 (30.9) 22 (34.4) 20 (25.0) and means ± SD.
Oral anticoagulants 28 (7.5) 5 (7.8) 4 (5.0)
Antihypertensives 144 (38.7) 27 (42.2) 27 (33.8)
Statins 68 (18.3) 11 (17.2) 14 (17.5)
Mean NIHSS score on
admission± SD* 7.4±6.4 14.0±6.9 10.0±6.9
Lesion location seizures, and 2 (10.0%) had generalized SE. None of the
Cortical* 159 (42.7) 46 (71.9) 26 (32.5) vascular risk factors had any effect on the risk of seizure
Leukoaraiosis 93 (25.0) 13 (20.3) 20 (25.0) occurrence, neither in the whole group nor in its two etio-
TOAST classification
Large artery disease 55 (14.8) 14 (21.9) logic subtypes. No IS subtype effect was detected (data not
Cardioembolism* 121 (32.5) 30 (46.9) shown). Medical and neurological complications appeared
Small vessel disease* 34 (9.1) 0 (0.0) to influence the propensity to develop ES. In particular, we
Other determined 28 (7.5) 5 (7.8) observed a lower burden of complications among stroke
Indeterminate 134 (36.0) 15 (23.4)
patients who did not develop ES in comparison with those
Data are expressed as means ± SD or numbers with percentages who developed ES (20 vs. 58.3%, for the subgroup of pa-
in parentheses. * p < 0.05. TOAST = Trial of Org 10172 in Acute tients with 0–2 complications), whereas patients with mul-
Stroke Treatment. tiple complications were significantly more represented in
a In women aged ≤45 years.
b In women aged >45 years. the subgroup with ES (30 vs. 4.2%, for the subgroup of pa-
tients with >6 complications, p < 0.001; table 3).
In the multivariate path analysis model, lesion type
was directly related to the development of complications
(mean difference, –0.66; 95% confidence interval,
seizures (13 patients). Hence, 516 patients with first-ever CI, –1.01 to –0.31 for IS vs. ICH). Both lesion type and
acute stroke were eligible for inclusion in the present study. stroke complications were directly related to the risk of
Of them, 436 (84.5%) had IS [64 (14.6%) with HT], 80 seizure occurrence (OR, 0.24; 95% CI, 0.07–0.80 for IS vs.
(15.6%) had ICH. The general characteristics of the study ICH, and OR, 1.57; 95% CI, 1.21–2.01 for any increase of
group by stroke subtype are summarized in table 2. 1 in the number of complications during the first week)
ES were observed in 20 patients (3.9%), 8 with ICH while changes in stroke severity had no significant direct
(10.0%), 12 with IS (2.4%; p < 0.001). Thirteen (65.0%) pa- effect on ES. Lesion site was also directly related to ES risk
tients had simple focal seizures (9 focal motor seizures; 6 (OR, 0.15; 95% CI, 0.04–0.56 for subcortical lesions vs.
with secondary generalization), 5 (25.0%) had generalized cortical lesions). Complications appeared to mediate the
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indirect effect of lesion type on stroke severity (mean dif-
ference, +0.98; 95% CI, +0.44 to +1.51 average NIHSS
changes of IS vs. ICH) and on the occurrence of ES (OR,
0.75; 95% CI, 0.60–0.94). No significant difference on the
risk of ES was observed when HT and ICH were com-
pared. The path model suggests a total effect of lesion type
equal to 0.24 × 0.75 = 0.18 (for IS vs. ICH) on the risk of
ES, that is, the total risk of ES was (1 – 0.18) = 82% lower
for IS as compared to ICH. Overall, the path selected
based on our data implicates that stroke subtypes have
both a direct effect and an indirect effect on the risk of ES,
the latter mediated by acute stroke complications, and
that lesion site has a direct effect on such a risk.
Discussion
Seizures are among the most common neurologic
consequences of stroke. Despite this evidence, the cur-
rent understanding of the pathophysiology of post-stroke
seizures remains incomplete, and it is still uncertain
whether or not seizures per se worsen the outcome of
acute stroke. ES in penumbral areas of cerebral ischemia
might be harmful because of the additional metabolic
stress they may cause in already vulnerable tissue [15].
Repeated seizure-like activities in the setting of experi-
mental stroke significantly increase lesion size and im-
pair functional recovery [16]. The upregulation of proin-
flammatory mediators observed in experimental models
of epileptogenesis [17] further supports this view, while
numerous clinical reports point toward an increased
length of hospital stay and in-hospital mortality among
patients who develop seizures soon after stroke [1–3, 18,
19]. Therefore, though unproven, the detrimental effect
of post-stroke seizures on patient outcome seems bio-
logically plausible. From a clinical perspective, better
definition of factors placing patients at increased risk of
ES has obvious implications, since it might help in iden-
tifying those subjects who could benefit more from ther-
apies aimed at reducing epileptogenesis and seizure-re-
lated functional impairment. In this regard, our study
differs from previous analyses as it is the first to investi-
gate the impact of acute complications of stroke on the
development of ES. A first, confirmatory finding of our
analysis is that among patients with acute brain infarc-
tion or ICH the occurrence of ES is related to nonmodi-
fiable predictors, of which stroke severity on admission,
cortical involvement, and stroke subtype have the largest
impact. In line with others, we did not detect any asso-
ciation of ES with pre-existent stroke risk factors or with
448 Cerebrovasc Dis 2013;35:444–450
DOI: 10.1159/000348704
the presumed pathogenic mechanism of cerebral isch-
emia either. The new findings were that (1) predictable
and modifiable complications of stroke are important
determinants of post-stroke seizures, and (2) complica-
tions of acute stroke mediate the effect of nonmodifiable
predictors on the risk of ES. This prompts us to speculate
that early identification and intensive management of
such complications has the potential of reducing the in-
cidence of post-stroke seizures and provides theoretical
explanations to the conflicting results of previous analy-
ses. In particular, a recent study conducted with the same
prospective design and similar patient selection criteria,
reporting data from stroke units and neurologic depart-
ments in Italy, found a 6.3% rate of ES, a figure slightly
higher than our estimates [20]. Since stroke complica-
tions were not recorded in that analysis, as in others [21–
29], however, we cannot rule out the possibility that such
discrepancies might depend on different rates of compli-
cations among the studies.
Strengths and Limitations
The strengths of our study were its prospective design,
the close observation of an unselected group of stroke pa-
tients from the first 24 h after onset in a well-established
and defined evidence-based stroke service, the applica-
tion of prespecified criteria for complications, and their
recording by a small number of trained health profession-
als. Furthermore, data were exclusively collected from pa-
tients admitted and treated in a single neurologic depart-
ment, which might improve the reliability of clinical data
and enhance the homogeneity of the sample.
There are also some limitations of our study that need
comments. Apart from the theoretical risk of selection
bias due to the hospital-based setting, and the inclusion of
only clinical seizures, like most of the studies conducted
so far, we are aware of shortcomings specific to our analy-
sis. First, we recorded only 12 preselected complications.
Although the effect of other undocumented complica-
tions, such as pain, falls, pressure sores/skin breaks or
deep vein thrombosis, might have been appropriate and
interesting to investigate, mostly because of the epilepto-
genic potential of drugs used to treat these conditions,
their impact on the occurrence of ES is expected to be
modest and it seems unlikely that they might have signif-
icantly altered the results of our study. Second, definition
of complications might also be a weakness and a further
factor that influenced our findings, even though all of our
definitions were similar to those used in most previous
complication studies [30, 31]. In particular, dichotomous
definitions as the ones we adopted in the present analysis
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do not allow speculation on whether the impact of such
complications might vary according to their severity. Fi-
nally, because of the observational design of the study we
cannot assess whether acute complications of stroke are
directly associated with ES or indirectly, as a consequence
of the proconvulsant effect of specific medications.
Implications
Our findings, if confirmed in independent data sets,
could improve the understanding of the mechanisms un-
derlying the occurrence of ES, a frequent complication of
patients with acute stroke, with the potential of increasing
the impact of stroke-related disability. Acute medical and
neurologic complications of stroke appear associated with
ES, and the strength of such a relationship seems different
in patients with ICH and in patients with IS. It is claimed
that much of the improvement in stroke outcomes in re-
cent decades is largely attributed to reducing and treating
complications more effectively [32]. Further studies test-
ing the effect that these complications might have on the
risk of ES and whether their impact on such a risk differs
according to stroke subtype could be important for pre-
ventive purposes to further improve stroke care.
Conclusions
Although nonmodifiable predictors, such as stroke se-
verity on admission, cortical involvement, and stroke
subtype, are major determinants of ES, preventable and
treatable complications within the first week of stroke
may also contribute or even mediate their effect. Future
epidemiologic studies aimed at investigating post-stroke
seizures should include precise information on these
complications.
Acknowledgements
We acknowledge Dr. Mauro Magoni, Unità Operativa di
Neurologia Vascolare, Spedali Civili di Brescia, and Dr. Daniela
Ferrari, Fondazione IRCCS Istituto Neurologico C. Besta, Mila-
no, who assisted in the ascertainment and recruitment of pa-
tients. We also express our gratitude to all the individuals who
participated in the study.
Disclosure Statement
None.

References
1 Silverman IE, Restrepo L, Mathews GC: Post-
stroke seizures. Arch Neurol 2002; 59: 195–
202.
2 Balami JS, Buchan AM: Complications of in-
tracerebral haemorrhage. Lancet Neurol
2012;11:101–118.
3 Balami JS, Chen RL, Grunwald IQ, Buchan
AM: Neurological complications of acute
ischaemic stroke. Lancet Neurol 2011; 10:
357–371.
4 Kumar S, Selim MH, Caplan LR: Medical co-
mplications after stroke. Lancet Neurol 2010;
9:105–118.
5 Krakow K, Sitzer M, Rosenow F, Steinmetz H,
Foerch C, Arbeitsgruppe Schlaganfall Hessen:
Predictors of acute poststroke seizures. Cere-
brovasc Dis 2010;30:584–589.
6 The European Stroke Organisation (ESO)
Executive Committee and the ESO Writing
Committee: Guidelines for management of
ischaemic stroke and transient ischaemic at-
tack 2008. Cerebrovasc Dis 2008; 25: 457–
507.
7 The European Stroke Initiative Writing Com-
mittee and the Writing Committee for the EUSI
Executive Committee. Recommendations for
the management of intracranial haemorrhage.
I. Spontaneous intracerebral haemorrhage.
Cerebrovasc Dis 2006;22:294–316.
8 Tissue plasminogen activator for acute isch-
emic stroke: the National Institute of Neurolog-
ical Disorders and Stroke rt-PA Stroke Study
Group. N Engl J Med 1995;333:1581–1587.
9 Wahlund LO, Barkhof F, Fazekas F, Bronge L,
Augustin M, Sjögren M, Wallin A, Ader H,
Leys D, Pantoni L, Pasquier F, Erkinjuntti T,
Scheltens P: A new rating scale for age-related
white matter changes applicable to MRI and
CT. Stroke 2001;32:1318–1322.
10 Wolpert SM, Bruckmann H, Greenlee R,
Greenlee R, Wechsler L, Pessin MS, del Zoppo
GJ, rtPA Acute Stroke Study Group: Neurora-
diologic evaluation of patients with acute
stroke treated with rtPA. AJNR 1993;14:3–13.
11 Berg AT, Berkovic SF, Brodie MJ, Buchhalter
J, Cross JH, van Emde Boas W, Engel J, French
J, Glauser TA, Mathern GW, Moshé SL, Nor-
dli D, Plouin P, Scheffer IE: Revised terminol-
ogy and concepts for organization of seizures
and epilepsies: report of the ILAE Commis-
sion on Classification and Terminology,
2005–2009. Epilepsia 2010;51:676–685.
12 Lowenstein DH, Bleck T, Macdonald RL: It’s
time to revise the definition of status epilepti-
cus. Epilepsia 1999;40:120–122.
13 Guidelines for epidemiologic studies on epi-
lepsy: Commission on Epidemiology and
Prognosis, International League against Epi-
lepsy. Epilepsia 1993;34:592–596.
14 Shipley B: Cause and Correlation in Biology.
A User’s Guide to Path Analysis, Structural
Equations and Causal Inference. Cambridge,
Cambridge University Press, 2000, pp 65–
130.
15 Reith J, Jorgensen HS, Nakayama H, Raas-
chou HO, Olsen TS: Seizures in acute stroke:
predictors and prognostic significance. The
Copenhagen Stroke Study. Stroke 1997; 28:
1585–1589.
16 Williams AJ, Lu XM, Slusher B, Tortella FC:
Electroencephalogram analysis and neuro-
protective profile of the N-acetylated-alpha-
linked acidic dipeptidase inhibitor GPI 5232,
in normal and brain-injured rats. J Pharmacol
Exp Ther 2001;299:48–57.
17 Ravizza T, Balosso S, Vezzani A: Inflamma-
tion and prevention of epileptogenesis. Neu-
rosci Lett 2011;497:223–230.
18 Arboix A, Comes E, García-Eroles L, Massons
JB, Oliveres M, Balcells M: Prognostic value of
very early seizures for in-hospital mortality in
atherothrombotic infarction. Eur Neurol
2003;50:78–84.
19 Shinton RA, Gill JS, Melnick SC, Gupta AK,
Beevers DG: The frequency, characteristics
and prognosis of epileptic seizures at the onset
of stroke. J Neurol Neurosurg Psychiatry
1988;51:273–276.
192.167.25.252 - 7/15/2013 1:59:08 PM
Univ.degli Studi di Brescia

Post-Stroke Seizures Cerebrovasc Dis 2013;35:444–450 449

DOI: 10.1159/000348704
Downloaded by:
20 Beghi E, D’Alessandro R, Beretta S, Consoli
D, Crespi V, Delaj L, Gandolfo C, Greco G, La
Neve A, Manfredi M, Mattana F, Musolino R,
Provinciali L, Santangelo M, Specchio LM,
Zaccara G, Epistroke Group: Incidence and
predictors of acute symptomatic seizures after
stroke. Neurology 2011;77:1785–1793.
21 Labovitz DL, Hauser WA, Sacco RL: Preva-
lence and predictors of early seizure and sta-
tus epilepticus after first stroke. Neurology
2001;57:200–206.
22 Bladin CF, Alexandrov AV, Bellavance A,
Bornstein N, Chambers B, Coté R, Lebrun L,
Pirisi A, Norris JW, Seizures after Stroke
Study Group: Seizures after stroke. A pro-
spective multicenter study. Arch Neurol 2000;
57:1617–1622.
23 Alberti A, Paciaroni M, Caso V, Venti M,
Palmerini F, Agnelli G: Early seizures in pa-
tients with acute stroke: frequency, predictive
factors and effect on clinical outcome. Vasc
Health Risk Manag 2008;4:715–720.
450 Cerebrovasc Dis 2013;35:444–450
DOI: 10.1159/000348704
24 Arboix A, García-Eroles L, Massons JB, Oli-
veres M, Comes E: Predictive factors of early
seizures after acute cerebrovascular disease.
Stroke 1997;28:1590–1594.
25 Lamy C, Domigo V, Semah F, Arquizan C,
Trystram D, Coste J, Mas JL, Patent Foramen
Ovale and Atrial Septal Aneurysm Study
Group: Early and late seizures after crypto-
genic ischemic stroke in young adults. Neu-
rology 2003;60:400–404.
26 Passero S, Rocchi R, Rossi S, Ulivelli M, Vatti
G: Seizures after spontaneous supratentorial
intracerebral hemorrhage. Epilepsia 2002; 43:
1175–1180.
27 Szaflarski JP, Rackley AY, Kleindorfer DO,
Khoury J, Woo D, Miller R, Alwell K, Broder-
ick JP, Kissela BM: Incidence of seizures in the
acute phase of stroke: a population-based
study. Epilepsia 2008;49:974–981.
28 Velioğlu SK, Ozmenoğlu M, Boz C, Alioğlu Z:
Status epilepticus after stroke. Stroke 2001;32:
1169–1172.
29 De Herdt V, Dumont F, Hénon H, Deram-
bure P, Vonck K, Leys D, Cordonnier C: Ear-
ly seizures in intracerebral hemorrhage. Inci-
dence, associated factors, and outcome. Neu-
rology 2011;77:1794–1800.
30 Davenport RJ, Dennis MS, Wellwood I, War-
low CP: Complications after acute stroke.
Stroke 1996;27:415– 420.
31 Langhorne P, Stott DJ, Robertson L, Mac-
Donald J, Jones L, McAlpine C, Dick F, Taylor
GS, Murray G: Medical complications after
stroke: a multicenter study. Stroke 2000; 31:
1223–1229.
32 Evans A, Perez I, Harraf F, Melbourn A,
Steadman J, Donaldson N, Kalra L: Can dif-
ferences in management processes explain
different outcomes between stroke unit and
stroke-team care? Lancet 2001; 358: 1586–
1592.
192.167.25.252 - 7/15/2013 1:59:08 PM
Univ.degli Studi di Brescia
Pezzini  et al.
Downloaded by: